Genetically stable cholera vaccines with deletions of ctxA, recA and attRS1
AssigneePresident and Felllows of Harvard College
InventorJohn J. Mekalanos
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Abstract
The invention features a nontoxigenic genetically stable mutant strain of V. cholerae which lacks any functional attRS1 sequences is useful as a live, oral vaccine for inducing immunological protection against cholera and a method for making same. The invention also features a killed, oral cholera vaccine comprising at least a first and a second V. cholerae strain, wherein at least one of the strains is a different serotype, and the vaccine also contains cholera toxin B subunit, produced by at least one of the serotypes.
Claims22
A nontoxinogenic genetically stable mutant strain of Vibrio cholerae, said strain comprising a genetically engineered deletion of DNA encoding ctxA subunit such that said strain lacks a reactogenic subunit A of cholera toxin, said strain further comprising deletions of attRS1 sequences, and having at least 1000-fold lower attRS1 mediated site-specific recombination relative to a parent strain having at least two copies of attRS1.
A method making a genetically stable mutant strain of Vibrio cholerae comprising a deletion of DNA encoding the ctxA subunit such that said strain lacks a reactogenic subunit A of cholera toxin, and said strain further comprising deletions of attRS1 sequences, said method comprising
- introducing into a wild type Vibrio cholerae a plasmid comprising a fragment of Vibrio cholerae DNA which is mutated in its ctxA and attRS1 sequences, said DNA being capable of recombining with wild type Vibrio cholerae DNA inside said wild type Vibrio cholerae resulting in the generation of said mutant strain, said mutant strain having at least 1000-fold lower attRS1 mediated site-specific recombination relative to a parent strain having at least two copies of attRS1.
Dependencies are inferred from the claim text.